This application proposes to collect DNA from 782 subjects participating in an ongoing longitudinal research project entitled "Lives across Time: A Prospective Study of Adolescent and Adult Development" (LAT) that was initiated in 1988. The collection of DNA, genotyping, and the testing of Gene X Environment (GE) interactions in the prediction of alcohol and depression phenotypes from adolescence to adulthood would enable the testing of gene-stressful environment relations within the context of a multivariate dynamic diathesis stress model. Distinctive features of the LAT include reasonably high retention rates across time (75%), seven-waves of data spanning critical transition points in the lifespan (e.g., adolescent-to-late young adulthood), a balance of male and female subjects, a broad battery of assessments on risk and protective factors, continuous and discrete (i.e., diagnostic) data for alcohol and depression phenotypes, the systematic and repeated assessment of stressful life events (SLEs). The DNA from the 782 adults will be used to conduct candidate gene analyses for GABRA2, GABRA1, CHRM2, CRHR1, CNR1, 5HTTLPR, and DRD2 for alcohol and depression phenotypes. GE interactions will be evaluated by specifying statistical models that incorporate both candidate gene and exposure variables (aggregated and disaggregated SLE measured at different phases of the lifespan) to predict alcohol and depression phenotypes across the long-term course of this study. The identification of significant GE interactions for alcohol and depressive disorders for specific genes and specific stressors occurring at different portions of the lifespan (e.g., adolescence, middle young adulthood) is of importance to public health because it will facilitate the targeting of tailored interventions that may be more successful in eliminating or ameliorating adverse health consequences associated with these disorders. PUBLIC HEALTH RELEVANCE: This two-year supplemental application proposes to collect DNA from 782 subjects participating in an ongoing longitudinal research project entitled "Lives across Time: A Prospective Study of Adolescent and Adult Development". Subsequent to genotyping the DNA for several candidate genes, genetic data will be integrated with the ongoing behavioral data collected in the parent grant to test gene-environment interactions within the context of a multivariate dynamic diathesis stress model.